msx1 transcription factor


Summary: A homeodomain protein that interacts with TATA-BOX BINDING PROTEIN. It represses GENETIC TRANSCRIPTION of target GENES and plays a critical role in ODONTOGENESIS.

Top Publications

  1. Gersch R, Lombardo F, McGovern S, Hadjiargyrou M. Reactivation of Hox gene expression during bone regeneration. J Orthop Res. 2005;23:882-90 pubmed
  2. Fallin M, Hetmanski J, Park J, Scott A, Ingersoll R, Fuernkranz H, et al. Family-based analysis of MSX1 haplotypes for association with oral clefts. Genet Epidemiol. 2003;25:168-75 pubmed
    ..This study encourages further focus on the MSX1 gene region to ultimately determine specific variants predisposing to oral clefts. ..
  3. Zhang Z, Zhang X, Avniel W, Song Y, Jones S, Jones T, et al. Malleal processus brevis is dispensable for normal hearing in mice. Dev Dyn. 2003;227:69-77 pubmed
    ..These results indicate that the malleal processus brevis is not necessary for sound transmission and seems dispensable for normal hearing and balance in mammals. ..
  4. Daikoku T, Cha J, Sun X, Tranguch S, Xie H, Fujita T, et al. Conditional deletion of Msx homeobox genes in the uterus inhibits blastocyst implantation by altering uterine receptivity. Dev Cell. 2011;21:1014-25 pubmed publisher
  5. Paixão Côrtes V, Braga T, Salzano F, Mundstock K, Mundstock C, Bortolini M. PAX9 and MSX1 transcription factor genes in non-syndromic dental agenesis. Arch Oral Biol. 2011;56:337-44 pubmed publisher
    ..Common variants located out of the DNA binding domain of the two PAX9 and MSX1 genes can also be related to tooth agenesis. ..
  6. Babajko S, Petit S, Fernandes I, Meary F, LeBihan J, Pibouin L, et al. Msx1 expression regulation by its own antisense RNA: consequence on tooth development and bone regeneration. Cells Tissues Organs. 2009;189:115-21 pubmed publisher
    ..In that sense, our current results suggest a clear involvement of Msx1 in alveolar bone. ..
  7. Ramos C, Robert B. msh/Msx gene family in neural development. Trends Genet. 2005;21:624-32 pubmed
    ..Finally, we will examine the distinct activities of Msx1, Msx2 and Msx3 genes during neurogenesis, taking into account their relationships with signalling molecules such as BMP. ..
  8. Han M, Yang X, Farrington J, Muneoka K. Digit regeneration is regulated by Msx1 and BMP4 in fetal mice. Development. 2003;130:5123-32 pubmed
    ..These studies provide the first functional analysis of mammalian fetal digit regeneration and identify a new function for Msx1 and BMP4 as regulators of the regenerative response. ..
  9. Mitchell L, Murray J, O BRIEN S, Christensen K. Evaluation of two putative susceptibility loci for oral clefts in the Danish population. Am J Epidemiol. 2001;153:1007-15 pubmed
    ..However, there is no evidence that the risk of CL+/-P or CP is influenced by gene-environment interactions involving MSX1 or TGFB3 and either first trimester exposure to maternal cigarette smoke or alcohol consumption. ..

More Information


  1. Hollnagel A, Oehlmann V, Heymer J, Ruther U, Nordheim A. Id genes are direct targets of bone morphogenetic protein induction in embryonic stem cells. J Biol Chem. 1999;274:19838-45 pubmed
    ..We therefore propose that the Msx and Id genes are direct target genes of embryonic BMP4 signaling in vivo. ..
  2. Yamagishi T, Nakajima Y, Miyazono K, Nakamura H. Bone morphogenetic protein-2 acts synergistically with transforming growth factor-beta3 during endothelial-mesenchymal transformation in the developing chick heart. J Cell Physiol. 1999;180:35-45 pubmed
    ..These results suggest that BMP2 1) plays an important role in the formation of endocardial cushion tissue and 2) acts synergistically with TGFbeta3 in the regulation of this developmental event. ..
  3. Reginelli A, Wang Y, Sassoon D, Muneoka K. Digit tip regeneration correlates with regions of Msx1 (Hox 7) expression in fetal and newborn mice. Development. 1995;121:1065-76 pubmed
    ..These data support the hypothesis that the expression of Msx genes are important for digit cells to initiate and participate in a regenerative response. ..
  4. Fu H, Ishii M, Gu Y, Maxson R. Conditional alleles of Msx1 and Msx2. Genesis. 2007;45:477-81 pubmed
    ..Analysis of progeny by PCR revealed correct Cre-mediated recombination, as well as expected phenotypes. ..
  5. Ma L, Lu M, Schwartz R, Martin J. Bmp2 is essential for cardiac cushion epithelial-mesenchymal transition and myocardial patterning. Development. 2005;132:5601-11 pubmed
    ..Our data indicate that Bmp2 has a crucial role in coordinating multiple aspects of AV canal morphogenesis. ..
  6. Ohazama A, Modino S, Miletich I, Sharpe P. Stem-cell-based tissue engineering of murine teeth. J Dent Res. 2004;83:518-22 pubmed
    ..These results thus provide a significant advance toward the creation of artificial embryonic tooth primordia from cultured cells that can be used to replace missing teeth following transplantation into the adult mouth. ..
  7. Bei M, Maas R. FGFs and BMP4 induce both Msx1-independent and Msx1-dependent signaling pathways in early tooth development. Development. 1998;125:4325-33 pubmed
  8. Berdal A, Lezot F, Pibouin L, Hotton D, Ghoul Mazgar S, Teillaud C, et al. Msx1 homeogene antisense mRNA in mouse dental and bone cells. Connect Tissue Res. 2002;43:148-52 pubmed
  9. Wang J, Jian F, Chen J, Wang H, Lin Y, Yang Z, et al. Sequence analysis of PAX9, MSX1 and AXIN2 genes in a Chinese oligodontia family. Arch Oral Biol. 2011;56:1027-34 pubmed publisher
    ..Our findings may imply that the PAX9 A240P mutation is a risk factor for oligodontia in the Chinese population. A240P is likely to be a genetic cause of oligodontia though previous literature suggested it as a polymorphism only. ..
  10. Bensoussan Trigano V, Lallemand Y, Saint Cloment C, Robert B. Msx1 and Msx2 in limb mesenchyme modulate digit number and identity. Dev Dyn. 2011;240:1190-202 pubmed publisher
    ..With this strategy, we demonstrate that mesenchymal expression of Msx1 and Msx2 is required for proper Shh and Bmp4 signaling to specify digit number and identity...
  11. Zhang Y, Zhang Z, Zhao X, Yu X, Hu Y, Geronimo B, et al. A new function of BMP4: dual role for BMP4 in regulation of Sonic hedgehog expression in the mouse tooth germ. Development. 2000;127:1431-43 pubmed
    ..Taken together, our data provide insight into a new regulatory mechanism for Shh expression, and suggest that this BMP4-mediated pathway in Shh regulation may have a general implication in vertebrate organogenesis...
  12. Catron K, Wang H, Hu G, Shen M, Abate Shen C. Comparison of MSX-1 and MSX-2 suggests a molecular basis for functional redundancy. Mech Dev. 1996;55:185-99 pubmed
    ..These features suggest that these members of the Msx family are 'equivalent but not equal' and that their proposed redundancy may be achieved via distinct biochemical mechanisms that yield a similar functional outcome. ..
  13. Vieira A, Meira R, Modesto A, Murray J. MSX1, PAX9, and TGFA contribute to tooth agenesis in humans. J Dent Res. 2004;83:723-7 pubmed
    ..No mutations were found in MSX1 or PAX9 coding regions. There were statistically significant data suggesting that MSX1 interacts with PAX9. These findings suggest that MSX1, PAX9, and TGFA play a role in isolated dental agenesis. ..
  14. Jumlongras D, Bei M, Stimson J, Wang W, DePalma S, Seidman C, et al. A nonsense mutation in MSX1 causes Witkop syndrome. Am J Hum Genet. 2001;69:67-74 pubmed
  15. Davidson D. The function and evolution of Msx genes: pointers and paradoxes. Trends Genet. 1995;11:405-11 pubmed
    ..Here, I review recent evidence that is beginning to address this problem and might eventually increase our understanding of how the vertebrate embryo has evolved. ..
  16. Lee H, Habas R, Abate Shen C. MSX1 cooperates with histone H1b for inhibition of transcription and myogenesis. Science. 2004;304:1675-8 pubmed
    ..Our findings define a previously unknown function for "linker" histones in gene-specific transcriptional regulation. ..
  17. Singh V, Ramu D. Association of MSX1 799?G>T variant with nonsyndromic cleft lip/palate in South Indian adolescent patients. Int J Paediatr Dent. 2012;22:228-31 pubmed publisher
    ..The results showed a positive correlation between MSX1 (799?G>T) gene variant and NSCLP patients. MSX1 (799?G>T) gene variants may be a good screening marker for NSCLP. ..
  18. Ogawa T, Kapadia H, Wang B, D Souza R. Studies on Pax9-Msx1 protein interactions. Arch Oral Biol. 2005;50:141-5 pubmed
    ..Our biochemical data, coupled with human genetic studies and expression analysis in a mouse model, indicate a functional relationship between Pax9 and Msx1 during tooth development. ..
  19. Peters H, Balling R. Teeth. Where and how to make them. Trends Genet. 1999;15:59-65 pubmed
    ..This cascade provides a molecular model by which reciprocal tissue interactions are controlled. ..
  20. Beaty T, Hetmanski J, Zeiger J, Fan Y, Liang K, VanderKolk C, et al. Testing candidate genes for non-syndromic oral clefts using a case-parent trio design. Genet Epidemiol. 2002;22:1-11 pubmed
    ..03). Using a conditional logistic model to test for gene-gene interaction showed no evidence of interaction between TGFbeta3 and MSX1, with both seeming to contribute independently to risk of isolated, non-syndromic oral clefts. ..
  21. Houzelstein D, Cheraud Y, Auda Boucher G, Fontaine Pérus J, Robert B. The expression of the homeobox gene Msx1 reveals two populations of dermal progenitor cells originating from the somites. Development. 2000;127:2155-64 pubmed
    ..The gene is downregulated prior to the onset of dermis differentiation, suggesting a role for Msx1 in the control of this process. ..
  22. Houzelstein D, Cohen A, Buckingham M, Robert B. Insertional mutation of the mouse Msx1 homeobox gene by an nlacZ reporter gene. Mech Dev. 1997;65:123-33 pubmed
    ..Notably, whereas the expression of Msx1 and Msx2 overlap in the developing limb, this is not the case in the facial regions most affected in the mutant. ..
  23. Kim J, Simmer J, Lin B, Hu J. Novel MSX1 frameshift causes autosomal-dominant oligodontia. J Dent Res. 2006;85:267-71 pubmed
  24. Stelnicki E, Kömüves L, Holmes D, Clavin W, Harrison M, Adzick N, et al. The human homeobox genes MSX-1, MSX-2, and MOX-1 are differentially expressed in the dermis and epidermis in fetal and adult skin. Differentiation. 1997;62:33-41 pubmed
    ..Furthermore, MOX-1 expression was completely absent in adult cutaneous tissue. These data imply that each of these homeobox genes plays a specific role in skin development. ..
  25. Bendall A, Ding J, Hu G, Shen M, Abate Shen C. Msx1 antagonizes the myogenic activity of Pax3 in migrating limb muscle precursors. Development. 1999;126:4965-76 pubmed
    ..Our results implicate functional antagonism through competitive protein-protein interactions as a mechanism for regulating the differentiation state of migrating cells. ..
  26. Venza I, Visalli M, Parrillo L, De Felice M, Teti D, Venza M. MSX1 and TGF-beta3 are novel target genes functionally regulated by FOXE1. Hum Mol Genet. 2011;20:1016-25 pubmed publisher
    ..Our findings give new insights into the genetic mechanisms underlying the Bamforth-Lazarus syndrome-associated facial defects. ..
  27. van den Boogaard M, Dorland M, Beemer F, van Amstel H. MSX1 mutation is associated with orofacial clefting and tooth agenesis in humans. Nat Genet. 2000;24:342-3 pubmed
  28. Bei M, Kratochwil K, Maas R. BMP4 rescues a non-cell-autonomous function of Msx1 in tooth development. Development. 2000;127:4711-8 pubmed
  29. Vieira A, Orioli I, Castilla E, Cooper M, Marazita M, Murray J. MSX1 and TGFB3 contribute to clefting in South America. J Dent Res. 2003;82:289-92 pubmed
    ..These results suggest that MSX1 and TGFB3 mutations make a contribution to clefts in South American populations. ..
  30. Mitsiadis T, Angeli I, James C, Lendahl U, Sharpe P. Role of Islet1 in the patterning of murine dentition. Development. 2003;130:4451-60 pubmed
    ..5 when tooth shape specification has passed to the mesenchyme, Islet1 expression requires distal (presumptive incisor) mesenchyme. Islet1 thus plays an important role in regulating distal gene expression during jaw and tooth development. ..
  31. Orestes Cardoso S, Nefussi J, Hotton D, Mesbah M, Orestes Cardoso M, Robert B, et al. Postnatal Msx1 expression pattern in craniofacial, axial, and appendicular skeleton of transgenic mice from the first week until the second year. Dev Dyn. 2001;221:1-13 pubmed
    ..The present study suggests that these signalling pathways are jointly important throughout the entire lifetime with an exquisite site-specificity spatially related to early patterning. ..
  32. Blin Wakkach C, Lezot F, Ghoul Mazgar S, Hotton D, Monteiro S, Teillaud C, et al. Endogenous Msx1 antisense transcript: in vivo and in vitro evidences, structure, and potential involvement in skeleton development in mammals. Proc Natl Acad Sci U S A. 2001;98:7336-41 pubmed
  33. Tucker A, Al Khamis A, Sharpe P. Interactions between Bmp-4 and Msx-1 act to restrict gene expression to odontogenic mesenchyme. Dev Dyn. 1998;212:533-9 pubmed
  34. Orestes Cardoso S, Nefussi J, Lezot F, Oboeuf M, Pereira M, Mesbah M, et al. Msx1 is a regulator of bone formation during development and postnatal growth: in vivo investigations in a transgenic mouse model. Connect Tissue Res. 2002;43:153-60 pubmed
    ..Our data suggest that Msx1 play a role in a site-specific manner not only in early patterning but also in skeletal growth and modeling by acting on heterogenous bone cell populations. ..
  35. Khadka D, Luo T, Sargent T. Msx1 and Msx2 have shared essential functions in neural crest but may be dispensable in epidermis and axis formation in Xenopus. Int J Dev Biol. 2006;50:499-502 pubmed
    ..If Msx genes have important functions in epidermis or axial mesoderm induction, these functions must be shared with other regulatory proteins. ..
  36. Chung I, Han J, Iwata J, Chai Y. Msx1 and Dlx5 function synergistically to regulate frontal bone development. Genesis. 2010;48:645-55 pubmed publisher
    ..Furthermore, Dlx5 requires Msx1 for its expression in the context of frontal bone development. Our study shows that Msx1/Dlx5 interaction is crucial for osteogenic induction during frontal bone development...
  37. Chen Y, Ishii M, Sun J, Sucov H, Maxson R. Msx1 and Msx2 regulate survival of secondary heart field precursors and post-migratory proliferation of cardiac neural crest in the outflow tract. Dev Biol. 2007;308:421-37 pubmed
  38. Ferguson C, Tucker A, Sharpe P. Temporospatial cell interactions regulating mandibular and maxillary arch patterning. Development. 2000;127:403-12 pubmed
  39. De Coster P, Marks L, Martens L, Huysseune A. Dental agenesis: genetic and clinical perspectives. J Oral Pathol Med. 2009;38:1-17 pubmed publisher
    ..These new perspectives and future challenges in the field of identification of possible candidate genes involved in dental agenesis are discussed. ..
  40. Hecht J, Mulliken J, Blanton S. Evidence for a cleft palate only locus on chromosome 4 near MSX1. Am J Med Genet. 2002;110:406-7 pubmed
  41. Vastardis H, Karimbux N, Guthua S, Seidman J, Seidman C. A human MSX1 homeodomain missense mutation causes selective tooth agenesis. Nat Genet. 1996;13:417-21 pubmed
    ..We propose that the Arg31 Pro mutatrion comprises MSX1 interactions, and suggest that MSX1 functions are critical for normal development of specific human teeth. ..
  42. Han J, Mayo J, Xu X, Li J, Bringas P, Maas R, et al. Indirect modulation of Shh signaling by Dlx5 affects the oral-nasal patterning of palate and rescues cleft palate in Msx1-null mice. Development. 2009;136:4225-33 pubmed publisher
    ..Our study shows that modulation of Shh signaling may be useful as a potential therapeutic approach for rescuing cleft palate...
  43. Lallemand Y, Bensoussan V, Cloment C, Robert B. Msx genes are important apoptosis effectors downstream of the Shh/Gli3 pathway in the limb. Dev Biol. 2009;331:189-98 pubmed publisher
  44. Ruhin Poncet B, Ghoul Mazgar S, Hotton D, Capron F, Jaafoura M, Goubin G, et al. Msx and dlx homeogene expression in epithelial odontogenic tumors. J Histochem Cytochem. 2009;57:69-78 pubmed publisher
    ..Based on the established roles of Msx and Dlx transcription factors in dental cell fates, these data suggest that their altered expression is a proposed trail to explain the genesis and/or the progression of odontogenic tumors. ..
  45. Zhang H, Catron K, Abate Shen C. A role for the Msx-1 homeodomain in transcriptional regulation: residues in the N-terminal arm mediate TATA binding protein interaction and transcriptional repression. Proc Natl Acad Sci U S A. 1996;93:1764-9 pubmed
  46. Xuan K, Jin F, Liu Y, Yuan L, Wen L, Yang F, et al. Identification of a novel missense mutation of MSX1 gene in Chinese family with autosomal-dominant oligodontia. Arch Oral Biol. 2008;53:773-9 pubmed publisher
    ..347C>G. Our finding suggests the missense transversion (c.662C>A) and the polymorphisms (c.347C>G) may be responsible for oligodontia phenotype in this Chinese family. ..
  47. Lee H, Quinn J, Prasanth K, Swiss V, Economides K, Camacho M, et al. PIAS1 confers DNA-binding specificity on the Msx1 homeoprotein. Genes Dev. 2006;20:784-94 pubmed
  48. Guha U, Gomes W, Kobayashi T, Pestell R, Kessler J. In vivo evidence that BMP signaling is necessary for apoptosis in the mouse limb. Dev Biol. 2002;249:108-20 pubmed
    ..These abnormalities were rescued by coexpressing BMP4 under the same promoter in double transgenic mice, suggesting that the limb abnormalities are a direct effect of inhibiting BMP signaling. ..
  49. Furuta Y, Piston D, Hogan B. Bone morphogenetic proteins (BMPs) as regulators of dorsal forebrain development. Development. 1997;124:2203-12 pubmed
    ..These results provide evidence that BMPs function during regional morphogenesis of the dorsal telencephalon by regulating specific gene expression, cell proliferation and local cell death. ..
  50. Galle S, Yanze N, Seipel K. The homeobox gene Msx in development and transdifferentiation of jellyfish striated muscle. Int J Dev Biol. 2005;49:961-7 pubmed
    ..This study indicates that the Msx protein may be a key component of the reprogramming machinery responsible for the extraordinary transdifferentation and regeneration potential of striated muscle in the hydrozoan jellyfish. ..
  51. Zhang H, Hu G, Wang H, Sciavolino P, Iler N, Shen M, et al. Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism. Mol Cell Biol. 1997;17:2920-32 pubmed
    ..Based on these observations, we propose that functional antagonism through heterodimer formation provides a mechanism for regulating the transcriptional actions of Msx and Dlx homeoproteins in vivo. ..
  52. Mackenzie A, Purdie L, Davidson D, Collinson M, Hill R. Two enhancer domains control early aspects of the complex expression pattern of Msx1. Mech Dev. 1997;62:29-40 pubmed
    ..However, the proximal element which produced expression in superficial nasal epithelium, dorsal and ventral myotome, limb mesenchyme, eye, ear, roof plate, second arch, genital ridge and epiphysis, was contained in only 78 bp. ..
  53. Nieminen P, Kotilainen J, Aalto Y, Knuutila S, Pirinen S, Thesleff I. MSX1 gene is deleted in Wolf-Hirschhorn syndrome patients with oligodontia. J Dent Res. 2003;82:1013-7 pubmed
    ..Our result confirms that haploinsufficiency for MSX1 serves as a mechanism that causes selective tooth agenesis but, alone, is not enough to cause oral clefts. ..